ABSTRACT
BACKGROUND: Lung transplantation is an acceptable and potentially life-saving treatment option for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome and pulmonary fibrosis. This study was conducted to determine whether recipients of lung transplantation (LT) for COVID-19-related lung disease have comparable outcomes to other recipients with a similar level of lung dysfunction. METHODS: The Organ Procurement and Transplant Network database was queried for adult LT candidates between 2006 and 2021. Recipients with COVID-19-related respiratory failure were matched 1:2 using a nearest-neighbor algorithm. Kaplan-Meier methods with log-rank tests were used to compare long-term survival. A proportional hazards model was used to calculate risk of death. RESULTS: A total of 37,333 LT candidates from all causes were compared with 334 candidates from COVID-19-related respiratory failure. COVID-19 recipients were more likely to be younger (50 vs 57 years, P < .001), male (79% vs 60%, P < .001), require extracorporeal membrane oxygenation (56.3% vs 4.0%, P < .001), and have worse lung function (lung allocation score, 82.4 vs 47.8; P < .001) at transplantation. Subsequently, 227 COVID-19 recipients were matched with 454 controls. Patients who received a transplant for COVID-19 had similar rates of mechanical ventilation, extracorporeal membrane oxygenation, postoperative complications, and functional status at discharge compared with controls. There was no difference in overall survival or risk of death from COVID-19 (hazard ratio, 0.82; 95% CI, 0.45-1.53; P = .54). CONCLUSIONS: Six-month survival for recipients of LT for COVID-19-related respiratory failure was comparable to that of other LT recipients.
ABSTRACT
BACKGROUND: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. MATERIALS AND METHODS: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. FINDINGS: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. INTERPRETATION: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.